DIFFERENTIAL METABOLISM OF DIETARY FATTY ACIDS

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our Preliminary Data in young, non-obese, human subjects suggest that increasing dietary palmitic acid (PA) over a period of 28-d lowers daily non-resting energy expenditure, blunts the usual post-exercise rise in energy expenditure, and lowers fatty acid (FA) oxidation in the fed state. Conversely, we found that increasing dietary oleic acid (OA) enhances FA oxidation and increases non-resting energy expenditure. However, it is important to determine if this effect can be seen within days of the diet or whether marked changes in membrane lipid composition are required. This question has relevance to the design of future studies, where subjects could be their own control. Also, as a consequence of their opposite effects on fat oxidation, PA and OA may in turn have contrasting effects on intramyocyte lipid concentration, which could affect insulin signaling in that tissue. Recent work at the Duke University Stedman Center by Dr. Muoio and others (1) has shown how metabolic screening (acyl-carnitine and acyl-CoA profiling) can be used both to address hypothesized mechanisms, and to reveal unexpected relationships that prompt new and/or alternative hypotheses. In particular, this work has demonstrated that techniques, previously used to presumptively diagnose inborn errors of FA metabolism, can be used to provide data on particular biochemical pathways that can be altered by changes in the capacity for FA oxidation. As part of an overall plan to gather preliminary data for a related NIH application, submitted on 2/1/05, we will collect muscle tissue for analysis of acyl-carnitine and acyl-CoA by Dr. Muoio at the Stedman Center. To explore these issues, a double-masked randomized, parallel groups, controlled feeding trial (7d) is proposed in 24 healthy, non-obese, adults, 18-40 yr of age examining the effects of two real food diets, differing in the relative concentrations of PA and OA. Two Specific Aims will be carried out: 1. To determine if increasing the PA content of the diet decreases fat oxidation in the fed state compared to a diet with lower PA and much higher OA. 2. To determine if raising the PA content of the diet increases the triacylglycerol (TAG) and diacylglycerol (DAG) content of muscle and alters the cardiolipin content of muscle, the fatty acid composition of phospholipids in muscle and adipose tissue, and the acyl-carnitine and acyl-CoA profile of skeletal muscle. This project will provide novel data in non-obese, non-diabetic humans on the effects of PA and OA, the two most common FA in the diet, on fat oxidation and muscle lipids. This study will have particular relevance to the prevention of insulin resistance, diabetes, and obesity.